# Vaginal Clinical Isolates of Candida albicans Differentially Modulate Complosome Activation in Vaginal Epithelial Cells

## TL;DR

This study shows that different strains of Candida albicans affect immune responses in vaginal cells differently, with one strain evading immune detection.

## Contribution

The study reveals a novel immune evasion strategy by a Candida albicans strain through modulation of complosome activity in vaginal epithelial cells.

## Key findings

- Colonizing C. albicans strain increases C3a release while VVC strain reduces C5 and C5a in vaginal epithelial cells.
- VVC strain reduces cathepsin D activity and C5aR1 levels, suggesting immune evasion.
- Colonizing strain increases intracellular C5aR1 without affecting C3aR levels.

## Abstract

The complosome controls different activities in innate immune cells and epithelial cells; however, its role in the response of VECs to Candida remains untested. In this in vitro study, we compared two clinical vaginal strains of C. albicans, namely, a Colonizing strain from a healthy woman and a strain from a patient with vulvovaginal candidiasis (VVC), for their ability to activate the complosome and release anaphylatoxins in vaginal epithelial cells (VECs). Our results show the following: (i) both strains triggered the cleavage of C3 into C3a and C3b within VECs, while infection with the Colonizing strain led to greater release of the anaphylatoxin C3a; (ii) infection with the VVC isolate led to a strong reduction in both C5 and C5a in VECs, while no increase in C5a release was observed after infection with either strain; (iii) cathepsin-family gene expression and cathepsin D activity were reduced in VECs infected with the VVC strain but not in those infected with the Colonizing strain; (iv) infection with the Colonizing strain induced a significant increase in intracellular C5aR1 while intracellular C3aR levels remained unchanged. Collectively, our data suggests the propensity of this VVC strain to inactivate the C5/C5aR1 axis and to reduce the C3/C3aR axis, dampening the activity of the complosome in VECs. These effects exerted by the VVC strain suggest a novel strategy of immune evasion by C. albicans and may open new perspectives for finding new therapeutic targets against vaginal fungal infections.